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PubMed1993

Detection of aneuploidy and possible deletion in paraffin-embedded rhabdomyosarcoma cells with FISH.

Conventional cytogenetic studies of solid tumors are limited by the difficulty of culturing tumor cells, while in situ hybridization using paraffin sections of interphase cells results in too many truncated cells. To solve these problems, fluorescent in situ hybridization (FISH) technique was used on free nuclei isolated from formalin-fixed paraffin-embedded embryonal rhabdomyosarcoma (RMS) tissue using our modification of Hedley's method for isolation of nuclei. Biotinylated DNA probes for the centromeric regions of chromosomes 6, 8, 11, 12, 17, and 18, painting probes for chromosomes 8 and 11, and a cosmid probe for the HER-2/neu oncogene, were used. The centromeric probes worked well, demonstrating two copies of chromosomes 6, 17, and 18, but three copies of chromosome 11 in 52.9% of nuclei. Four copies of chromosome 8 were observed in 57.1% of nuclei and five or more in 17.1%. Chromosome 12 demonstrated 21.8% trisomy and 62.2% tetrasomy. Painting probes for chromosome 11 also worked well and matched the results of the centromeric probes, with no suggestion of structural aberration. However, the results of the painting probe for chromosome 8 yielded fluorescent areas of different sizes, suggesting that some of the extra chromosomes 8 could be deleted. The cosmid probe for the HER-2/neu oncogene also worked well, and revealed two signals in each nucleus without evidence of amplification. This study illustrates the successful use of a new technique for studying chromosomal aberration in paraffin-embedded solid tumors. The importance of this technique is that it has not been previously possible to use painting probes or cosmid probes on paraffin tissue sections. Use of this procedure will broaden the type of retrospective studies that can be performed to include detection of deletions or translocations.

Aged↗
PubMed1993

Rhabdomyosarcoma. A cytogenetically interesting case report.

Chromosomal analysis was performed on the tumor tissue in a case of ocular rhabdomyosarcoma. Cytogenetic analysis revealed multiple clonal abnormalities. Derivative(5)t(1;5)(q21;q35) and t(2;11) (q21;q23) were present in all the metaphases analyzed (100%). Translocation(1;19)(q21;q13) was observed in 61% of the metaphases. Other clonal abnormalities present included +i(6p)(85%),i(17q)(38%),18q+(57%), 4p+ (38%), loss of the Y chromosome (33%), and presence of double minutes (12.8%).

Child, Preschool↗
PubMed1988

Therapy of rhabdomyosarcoma of the larynx.

A case of subglottic rhabdomyosarcoma in a 13-year-old boy is reported. Following partial conservative resection of the larynx with supplementary chemotherapy and without irradiation, the patient has had no functional impairment of the larynx and has shown no evidence of recurrence for more than 3 years.

Adolescent↗
PubMed1988

Interstitial hyperthermia using 27 MHz wire antennas and interstitial photodynamic therapy in a rat rhabdomyosarcoma: phantom and animal studies.

This paper deals with the interaction of interstitial hyperthermia (HT) and interstitial photodynamic therapy (PDT). Its main focus, however, is on a newly developed heating system; phantom studies as well as temperature-response data obtained from the in vivo experiments are presented. Heat was delivered by thin, flexible wire antennas operating at a frequency of 27 MHz. Measurements in muscle-equivalent phantom with infrared thermography were performed. Uniform heating over the inserted length of the antenna was obtained and impedance matching appears possible by simple variable air coils, thereby minimizing the reflected power to less than 20%. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a total incident dose of 900 J from four linear light applicators. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of haematoporphyrin derivative (HPD), Photofrin II, was injected intravenously. The tumors were subsequently implanted with four flexible catheters, through which either light or heat could be applied. Dose-response relationships for PDT alone, HT alone and PDT followed by HT were established with cure as endpoint. The animal experiments showed that with the use of low-frequency wires a good localized heat distribution in the tumors can be obtained. Moreover, this study showed that PDT and HT, in the proper sequence and only when optimal temperatures are reached, result in an augmented cytotoxicity on the tumor cells in vivo; i.e. a cure rate of 41% was obtained.

Animals↗
PubMed1992

Radiotherapy of the rhabdomyosarcoma R1H of the rat: recovery from radiation injury in tumour and skin.

The response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation has been reported to be almost independent of the dose per fraction in the range from 0.43 to 10 Gy. To elucidate whether recovery from radiation injury is impaired in fractionated irradiation or not, tumours were exposed on 5 days per week over 6 weeks either to a single daily dose or to two daily fractions separated by an interfraction interval of 2 h. Tumour response was assessed by net growth delay. Skin damage was scored for comparison. A significant reduction in tumour response (p less than 0.009) and skin damage (p less than 0.001) was observed when the daily dose was administered in a twice daily irradiation regimen, indicating that recovery from radiation injury does occur in the course of fractionated irradiation in our tumour system. A tumour response was almost independent of the dose per fraction for time intervals between fractions of at least 8 h, a possible explanation might be that recovery is compensated by improved reoxygenation.

Animals↗
PubMed1994

Radiotherapy of the rhabdomyosarcoma R1H of the rat: influence of the time interval between two daily fractions during hyperfractionated radiotherapy.

The response of the rhabdomyosarcoma R1H of the rat to hyperfractionated irradiation with different time intervals between the two daily fractions has been investigated. All tumours were exposed to irradiation 5 days per week over 6 weeks. A standard treatment of 30 fractions, i.e. one fraction per day, of 1.83-2.75 Gy (200 kVp X-rays) was compared with a hyperfractionated schedule of 60 fractions, i.e. two fractions per day, of 0.92-1.38 Gy with time intervals of either 1, 2, 3, 5 or 6 h between the two daily fractions. Tumour response has been assessed by (a) net growth delay and (b) local tumour control. Compared with standard treatment (one fraction per day) significant reduction (p < 0.005) of net growth delay was observed for the tumours treated with two daily fractions separated by 2 h. However, at a time interval of 5 and 6 h between the two daily fractions net growth delay increased considerably (p < 0.0001 and p < 0.01) as compared with the standard treatment and an increased rate of local tumour control was observed. The major findings is that tumour response is not as would be predicted by repair if the interval between the two daily fractions exceeds 2 h. The competing or overriding mechanisms cannot be identified ultimately, but the data, though based on small animal numbers and collected over an extended time period, reflect a significant effect.

Animals↗
PubMedDate not supplied

Rhabdomyosarcoma of the infratemporal fossa: diagnostic dilemmas and surgical management.

We present a rare case of embryonal rhabdomyosarcoma in the infratemporal fossa presenting as an atypical facial pain syndrome. Radiographic imaging of the patient is discussed, and magnetic resonance imaging is recommended as the diagnostic modality of choice when mass lesions of the infratemporal fossa are suspected. Finally, a temporal approach to the infratemporal fossa is described, along with its advantages as an application for tumor resection in this anatomic region.

Child↗
PubMed1994

Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA-HAN-1C.

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. This cell line has been shown to be susceptible to differentiation induction with all-trans retinoic acid (RA). Since it is still unknown whether exclusively all-trans RA itself or also its metabolites can act as inductive compounds in our cell line, we exposed BA-HAN-1C cells to the metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA. Exposure to these RA metabolites resulted in a significant inhibition of proliferation (P < 0.001) and induction of cellular differentiation, as evidenced by a significant increase in the number of myotube-like giant cells (P < 0.05) and a significant increase in creatine kinase activity (P < 0.05). However, differences in the inductive potency of these RA metabolites became apparent. Furthermore, RA metabolites exhibited a significantly weaker (P < 0.05) inductive activity when compared to all-trans RA. Summarizing our results we could demonstrate that the endogenous metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA are not merely deactivated cellular excretion products of all-trans RA, but potent inducers of differentiation and inhibitors of proliferation, possibly contributing to the complex physiological actions of retinoic acid.

Animals↗
PubMed1984

Childhood rhabdomyosarcoma xenografts: responses to DNA-interacting agents and agents used in current clinical therapy.

A laboratory model of childhood rhabdomyosarcoma (RMS) has been used to evaluate cytotoxic agents used in current clinical protocols, and DNA-reacting agents that have had either limited or no evaluation in this histiotype. Seven lines of RMS each derived from a different patient were grown as xenografts in immune-deprived mice, six of these being from specimens derived from previously untreated patients. Of the 'conventional' agents, vincristine was the most effective. Of the other agents evaluated [L-phenylalanine mustard (L-PAM), cis-dichlorodiammineplatinum (cis-DDP), mitomycin C and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC)], L-PAM caused complete regressions in six of seven lines, including those resistant to cyclophosphamide. DTIC had marked activity in five tumors, and mitomycin C in three lines. Cyclophosphamide was active in five tumors, although efficacy was less marked in two lines in comparison to DTIC and mitomycin C.

Animals↗
PubMed1989

Quantitative transplantation assays of the rat rhabdomyosarcoma BA1112 isografts into the WAG/Rij Y rat and xenotransplantation into the athymic NCr (nu/nu) nude mouse.

Quantitative tumor cell transplantation assays have been performed to compare the transplantability of rat rhabdomyosarcoma BA1112 into isologous WAG/Rij Y rats and athymic NCr(nu/nu) nude mice. The end-point was the TD50 or the number of viable tumor cells which would transplant the tumors into half of the recipients. At Yale, two sets of 2-fold dilutions were prepared, one was sent to the MGH by Air Express. That afternoon, concurrent assays were performed at Yale using the WAG/Rij Y rat and at MGH using the NCr(nu/nu) mouse. The TD50 values were the same for iso- and xenotransplantation. Furthermore, the TD50s in rats and mice were unaffected by standard immunization procedures prior to challenge of the TD50 assay. The BA1112 (10(7) trypan blue excluding cells) grew to 10-12 mm and then completely regressed if transplanted into NCr(nu/+) mice which had received 6 Gy whole body irradiation but did not grow in control NCr(nu/+) mice. The times for the BA1112 to grow to 10 mm were the same in normal or preimmunized WAG/Rij Y rats or NCr(nu/nu) mice and in 6 Gy WBI NCr(nu/nu) mice. All of the experimental data show that the xenogenic NCr(nu/nu) mice accept the BA1112 as readily as do the isologous WAG/Rij Y rats.

Animals↗
PubMed1988

Embryonal rhabdomyosarcoma arising in the masseter muscle as a second malignant neoplasm.

A case is reported about a patient who was originally treated for bilateral retinoblastoma and subsequently developed an embryonal rhabdomyosarcoma in the masseter. Such patients have a genetic predisposition to a second malignancy that statistically far exceeds the rate for the general population. In addition, current treatment methods also increase the patient's susceptibility to another malignancy. This case emphasizes the necessity of maintaining a high degree of clinical suspicion in the evaluation of any lesion that may appear subsequent to the treatment of cancer in children, particularly bilateral retinoblastoma.

Child↗
PubMed1988

Rhabdomyosarcoma of the maxillary sinus: review of the literature and report of a case.

A case of rhabdomyosarcoma of the maxillary sinus is reported. A brief review of the origin, histomorphology, classification, clinical presentation, behavior, prognosis, and treatment is given relative to occurrence in the maxillary antrum. Misinterpretation of the microscopic findings can delay the histologic diagnosis. An error in tissue diagnosis may be minimized by awareness of a chance encounter with this lesion.

Adult↗
PubMed1988

Influence of host age on lung colony forming capacity of injected rat rhabdomyosarcoma cells.

Intravenous administration of RA-2 transplantable rhabdomyosarcoma cells produces development of metastatic tumour cell colonies in the lungs of host rats. After administration of 2 X 10(3), 5 X 10(3) or 10 X 10(3) RA-2 cells, different patterns of dependence of the number of metastatic clones in the lungs on injected cell number have been observed. The numbers of tumour cell colonies were shown to be highest in immature (1-month-old) and old (15-month-old) female rats compared to middle-age groups (3- and 12-month-old). A similar age-related pattern was observed in male rats. Analysis of the results obtained has revealed positive correlation between tumour cell colony numbers and both somatomedin activity and proliferation rate of neoplastic tissue.

Age Factors↗
PubMed1993

Evidence that membrane proteins of rhabdomyosarcoma cell line RD bind human immunodeficiency virus type 1 (HIV-1).

Membrane proteins (MP) obtained from the human mesenchymal rhabdomyosarcoma cell line RD were coated on 96-well polystyrene microplates and tested for their ability to bind human immunodeficiency virus type 1 (HIV-1). The virus bound to MP was detected by solid phase assay. Anti-human CD4 monoclonal antibodies directed against the HIV-1 gp120 binding site of the CD4 receptor did not inhibit viral binding to MP. HIV-1 specific polypeptides were recovered from coated MP to microplates by a modification of the solid phase immunoisolation technique and shown by immunoblotting analysis using a high titer of biotinylated human anti-HIV-1 IgG. Together these findings provide evidence that HIV-1 binding to RD cell surfaces can proceed via a mechanism other than those mediated by the CD4 receptor.

Animals↗
PubMed1986

Cell surface glycosaminoglycans of rat rhabdomyosarcoma lines with different metastatic potentials and of non-malignant rat myoblasts.

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials and of non-malignant myoblasts, grown in the presence or in the absence of hydrocortisone, were studied comparatively. The newly formed [3H]glucosamine-labelled cell surface proteoglycans and glycosaminoglycans were separated by ion exchange chromatography and partially characterized. The overall incorporation of the label in the glycosaminoglycan fractions and the average molecular weight of the heparan and of the chondroitin sulfate proteoglycans was lower in the malignant cells than in the non-malignant L6 myoblasts. The strongly metastatic 9-4/0 parental line and the 6 subline were relatively richer in chondroitin sulfate and poorer in dermatan sulfate labels than the very weakly metastatic 8 subline and the L6 myoblasts. Hyaluronic acid and heparan sulfate labels were inversely related to the metastatic capacity of the cell lines studied. Hydrocortisone treatment induced an increase in the cell surface chondroitin and dermatan sulfate labels in the case of the strongly metastatic lines, and a decrease of the same parameters in the case of the weakly metastatic 8 line.

Animals↗
PubMed1985

Parameningeal rhabdomyosarcoma (including the orbit): results of orbital irradiation.

Twenty-three patients with parameningeal (including orbital rhabdomyosarcoma (RMS)) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and January 1983. Twenty were children with a mean age of 6 and 3 were adults. In 6 patients, the primary tumor was from the orbit, whereas the remaining 17 had other parameningeal primary sites. The tumors were in a very progressive local stage, with extensive destruction of the facial bones in 19 patients. Eight patients were treated with T2 chemotherapy protocol and 15 received T6. Seven patients received 5,000 to 7,200 rad delivered to the primary tumor in 11-16 weeks, 15 patients received between 4,500 to 5,000 rad in 4-7 weeks, and 1 patient received 3,000 rad in 3 weeks for residual microscopic disease following surgery. Two patients were treated with radiation to the whole brain; no patients received radiation of the whole central nervous axis (CNA). Fifteen of the 23 patients (65%) are alive and well with a medical follow-up time of 5 years. Two patients died of therapeutic complications and six died of tumor spread. In five patients, involvement of the central nervous system (CNS) was the cause of death. The prognosis of orbital RMS with parameningeal involvement is no better than in other tumors of parameningeal sites. In those patients who had impaired vision because of optic nerve damage prior to treatment, the vision did not improve following treatment. There was no impaired vision seen due to radiation damage of eye structures except in the lens.

Adolescent↗
PubMed1988

Interaction of interstitial photodynamic therapy and interstitial hyperthermia in a rat rhabdomyosarcoma--a pilot study.

Photodynamic therapy (PDT) involves the activation of photosensitizing drugs by light of appropriate wavelength. The photosensitive agent Hematoporphyrin Derivative (HPD) appears to be preferentially retained in malignant tumors; irradiation of HPD-containing tissue by light of appropriate wavelength (625 nm) and dose leads to (tumor) tissue destruction. The aim of this study is to achieve maximum tumor control probability with minimum normal tissue photosensitivity. In previous work from our laboratory it has been demonstrated that PDT has its fundamental effects on the tumor and normal tissue microcirculation. As it is well established that hyperthermia (HT) has its major effects in less well vascularized areas of the tumor, the combined modality of HT and PDT might prove to be advantageous. Moreover, suppression of sublethal damage repair by HT has been observed. To overcome the problem of poor light penetration into tissues and the high rate of recurrences following PDT with external irradiation, the combined effects of interstitial PDT with interstitial hyperthermia in a new line of animal experiments were studied in our laboratory. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of HPD, that is Photofrin II, was injected intravenously in different dose schedules (5 mg/kg, 10 mg/kg). After 24 or 48 hrs the tumors were implanted with four flexible catheters, through which either light or heat could be applied. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a dose level of 900 Joule from four linear light applicators. Heat (44 degrees C/30') was delivered by four 27 MHz radiofrequency antennas. Dose response relationships for PDT alone, HT alone and PDT combined with HT were established with cure as endpoint. This study showed that these two modalities, in the proper sequence and spacing, result in an augmented cytotoxicity on the tumor cells in vivo. With the combined modality treatment a cure rate of 41% (90 days) was obtained. As the implantation of flexible catheters is a well-known technique in radiation therapy practice, the potentiating effects of interstitial HT combined with interstitial PDT in solid tumors is very promising and clinical studies are warranted.

Animals↗